The dorsolateral periaqueductal grey N-methyl-D-aspartate/nitric oxide/cyclic guanosine monophosphate pathway modulates the expression of contextual fear conditioning in rats

Author(s)

Aguiar, Daniele C. ^[1] ; Hott, Sara C. ^{[2, 3]} ; Deolindo, Milena V. ^[2] ; Guimaraes, Francisco S. ^{[2, 3]} ; Resstel, Leonardo B. M. ^{[2, 3]}

Affiliation

^[1] Univ Fed Minas Gerais, Dept Pharmacol, Belo Horizonte, MG - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, BR-14049 Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF PSYCHOPHARMACOLOGY; v. 28, n. 5, p. 479-485, MAY 2014.
• Web of Science Citations: 7

Abstract

The dorsolateral periaqueductal grey (dlPAG) plays an essential role in unconditioned fear responses and could also be involved in the expression of contextual fear responses. Activation of glutamate N-methyl-D-aspartate (NMDA) receptors and the nitric oxide (NO) pathway in this region facilitates anxiety-like responses. In the present study we investigated if antagonism of NMDA receptors or inhibition of the NO pathway in the dlPAG would attenuate behavioral and cardiovascular responses of rats submitted to a contextual fear-conditioning paradigm. Male Wistar rats with unilateral cannulae aimed at the dlPAG were re-exposed to a chamber where they had received footshocks 48 h before. Ten min before the test the animals received an intra-dlPAG injection of vehicle, AP7 (NMDA receptor antagonist), N-propyl-L-arginine (neuronal NO synthase inhibitor), carboxy-PTIO (NO scavenger) or 1H-{[}1,2,4] oxadiazolol {[}4,3-a]quinoxalin-1-one (ODQ) (guanylate cyclase inhibitor). Freezing and cardiovascular responses were recorded continuously for 10 min. Intra-dlPAG administration of AP7 before re-exposure to the aversively conditioned context attenuated these responses. Similar effects were observed after the NO synthase inhibitor, NO scavenger or guanylate cyclase inhibitor. Our findings suggest that activity of dlPAG NMDA/NO/cyclic guanosine monophosphate (cGMP) pathway facilitates the expression of contextual fear responses. (AU)

• FAPESP's process: 11/07332-3 - Possible role of dorsal hippocampus on behaviour and autonomic responses during defensive responses: involvement of NMDA receptor/nitric oxide and endocanabinoid
• Grantee: Leonardo Resstel Barbosa Moraes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/09300-4 - Bed nucleus of the stria terminalis noradrenergic system modulates contextual fear conditionig: possible interaction with CRF and glutamatergic and nitrergic neurotransmission
• Grantee: Leonardo Resstel Barbosa Moraes
• Support Opportunities: Regular Research Grants